Objective To conduct a detailed clinical phenotypic analysis and gene mutation detection on an au-tosomal dominant Van der Hoeve syndrome family,and to identify the pathogenic gene mutation sites of the family and the impact of the mutation on gene coding.Methods Clinical data including medical history,physical examina-tion and auxiliary examination were collected and peripheral blood samples were collected from the Van der Hoeve syndrome families.Exome sequencing and Sanger sequencing were performed on 22 family members.The data were analyzed using bioinformatics software.Results The family had a total of 5 generations,with each generation expe-riencing consecutive illnesses.Each generation of men and women could suffer from the disease,which conformed to the characteristics of autosomal dominant inheritance.The 12 patients in this family were all born with blue sclera and short stature.8 patients had a history of fractures and could heal normally.3 patients were considering hearing loss caused by Van der Hoeve syndrome.12 patients had a base deletion(c.1128delT)in exon 17 of the COL1A1 gene,causing a change in the amino acid coding after position 376 and ending the amino acid coding prematurely at position 539.10 asymptomatic individuals in this family didn't had this mutation.Conclusion The patient of this family was identified as Van der Hoeve syndrome caused by c.1128 delT mutation.

The theory of "liver opens at the eyes" was first seen in Yellow Emperor's Internal Canon of Medicine， which is the ancient people's summary of the connection between the liver and the eyes. The theory of "liver opens at the eyes" suggests the characteristic of "co-damage and co-recover of liver and eyes". It has been found in clinical practice that liver diseases and eye diseases often occur together， and "liver and eyes co-recover" is an ideal choice. The key to achieving "liver and eyes co-recover" is to analyze its pharmacological material basis and mechanism. With the development of modern medicine， more and more evidence indicates that the liver and eyes have complex and close relationships in physiological and pathological aspects. In a pathological state， there is a phenomenon of "liver and eyes co-damage"， and after the intervention of traditional Chinese medicine， "liver and eyes co-recover" occurs. "Liver and eyes co-damage and co-recover" can be explained through the "co-material basis and co-action mechanism". On this basis， the research group tentatively proposed that the liver and eyes had "four common characteristics" （4CCs）， namely "co-damage， co-recover， co-material basis， and co-action mechanism" from the theoretical connotation of traditional Chinese medicine， clinical practice， and molecular biology. Additionally， the group also took the intervention of Prunella vulgaris， traditional Chinese medicine， for removing liver fire and improving eyesight on immune liver injury （ILI） and allergic conjunctivitis （AC） as examples to analyze 4CCs. This project aims to deeply analyze the scientific connotation of the theory of "liver opens at the eyes"， reveal the common characteristics and biological essence of liver and eyes， explore a new research paradigm of "liver and eyes co-recover"， and provide a reference for the study of common problems of multi-organ associated diseases.

Excessive N-acetyl-p-benzoquinone imine(NAPQI)formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen(APAP)overdose caused acute liver failure(ALF).S-glutathionylation is a reversible redox post-translational modification and a prospective mechanism of APAP hepatotoxicity.Glutaredoxin-1(Glrx1),a glutathione-specific thioltransferase,is a primary enzyme to catalyze deglutathionylation.The objective of this study was to explored whether and how Glrx1 is associated with the development of ALF induced by APAP.The Glrx1 knockout mice(Glrx1-/-)and liver-specific overexpression of Glrx1(AAV8-Glrx1)mice were produced and underwent APAP-induced ALF.Pirfenidone(PFD),a potential inducer of Glrx1,was administrated preceding APAP to assess its protective effects.Our results revealed that the hepatic total protein S-glutathionylation(PSSG)increased and the Glrx1 level reduced in mice after APAP toxicity.Glrx1-/- mice were more sensitive to APAP overdose,with higher oxidative stress and more toxic metabolites of APAP.This was attributed to Glrx1 deficiency increasing the total hepatic PSSG and the S-glutathionylation of cytochrome p450 3a 11(Cyp3a11),which likely increased the activity of Cyp3a11.Conversely,AAV8-Glrx1 mice were defended against liver damage caused by APAP overdose by inhibiting the S-glutathionylation and activity of Cyp3a11,which reduced the toxic metabolites of APAP and oxidative stress.PFD precede administration upregulated Glrx1 expression and alleviated APAP-induced ALF by decreasing oxidative stress.We have identified the function of Glrx1 mediated PSSG in liver injury caused by APAP overdose.Increasing Glrx1 expression may be investigated for the medical treatment of APAP-caused hepatic injury.

The successful retrieval of ancient mitochondrial DNA (mtDNA) from Neanderthals provides powerful experimental evidence that clarifies the arguments between the out-of-Africa and multiregional models of evolution. However, the lack of nuclear DNA from Neanderthal fossils and mtDNA of early modern human fossils dating back to approximately the same time in the Pleistocene constitutes a limitation that may compromise the significance of mtDNA phylogenetic analysis. In this report, we introduce a mitochromic analysis using Neanderthal mtDNA as a foreign transgene and humans as a naturally occurring transgenic species. Forty Neanderthal mtDNA retrievable nuclear fragments were identified by blasting human genome data with Neanderthal mtDNA. Five of the 40 fragments exhibited higher correlation with Neanderthal mtDNA than those with modern human mtDNA. Furthermore, these five nuclear fragments harbor Neanderthal mtDNA-unique haplotypes. Based on the 98%+ identity between Neanderthal and modern human mtDNA when compared by groups, we suggest that some of the modern human nuclear fragments retrieved using Neanderthal mtDNA may aid in decoding Neanderthal genetic information, and also may simultaneously demonstrate a close genetic evolutionary relationship between modern humans and Neanderthals.

Objective To verify that lncRNA-C21orF96 regulates the expression of miRNA-875-5p and USF2 genes and promotes the invasion and metastasis of gastric cancer.Methods RT-PCR was used to measure the expression of lncRNA-C21orF96 related miRNA in gastric cancer cells.pcDNA3.1 plasmid was used to over-express lncRNA-C21orF96 in KATO-Ⅲ and siRNA was used to knockdown the expression of lncRNA-C21orF96 in SGC-7901,and RT-PCR was used to measure the expression of miRNA-875-5p and USF2 genes;By overexpressing lncRNA-C21orF96 in MKN45,transwell was used to observe changes of cells invasion and migration.Results LncRNA-C21orF96 showed a significant inverse relationship with miR-875-5p,(SGC-7901:21.19 ±1.09 vs.3.28 ±0.06,P＜0.01;SNU-16:24.76 ±2.09 vs.8.16 ±0.07,P ＜ 0.01).In KATO-Ⅲ over-expressing lncRNA-C21 orF96,miR-875-5p expression decreased significantly while USF2 expression increased (P ＜0.01);In SGC-7901 with lncRNA-C21orF96 knockdown,miR-875-5p expression increased significantly while USF2 expression decreased (P ＜ 0.05).The number of cells passing through the artificial basement membrane in the experimental group was significantly different from that in the control group (migration:216.19 ± 2.30 vs.89.19 ± 4.60,P＜0.001;invasion:146.18 ±5.3 vs.59.18 ± 2.60,P ＜ 0.001).Conclusions The overexpression of lncRNA-C21orF96 significantly reduces the expression of miR-875-5p and promotes the expression of USF2,hence promoting the invasion and metastasis of gastric cancer.

OBJECTIVE：To establish a method for simultaneous determination of calycosin glucoside ，ononin，calycosin， formononetin，astragaloside Ⅳ，isoastragaloside Ⅱ，cycloastragenol and isoastragaloside Ⅰ in Astragalus membranaceus before and after bidirectional solid fermentation with Cordyceps kyushuensis ，and to investigate the effects of fermentation on the contents of above 8 components in A. membranaceus . METHODS ：HPLC-DAD-ELSD was adopted. The determination was performed on Agilent 5 TC-C18 column with mobile phase consisted of 0.1％ formic acid aqueous solution-acetonitrile （gradient elution ）at the flow rate of 1 mL/min. The column temperature was set at 30 ℃. DAD detection wavelength was set at 260 nm，ELSD evaporation tube temperature was 100 ℃，atomizer temperature was 80 ℃，carrier gas flow rate was 1.6 L/min；injection volume was 15 μL. RESULTS：The eight components had a good linear relationship within their respective ranges of concentration （all R2＞0.999 0）； RSDs of precision ，stability and repeatability tests were all less than 3％（n＝3 or n＝6）；the recoveries was 97.88％-101.32％， and RSDs were 1.22％-2.39％（n＝6）. Setting the content of components in unfermented A. membranaceus as 100％，after bidirectional solid fermentation with C. kyushuensis ，the change rates of 8 components were －98.51％，－96.41％，－94.74％， －96.40％，289.20％，20.25％，－75.05％，562.46％，respectively. CONCLUSIONS ：After fermentation with C. kyushuensis ，the contents of active components as astragaloside Ⅳ，isoastragaloside Ⅰ and isoastragaloside Ⅱ can be increased significantly in A. membranaceus .

Objective:To explore the effects of the process parameters of film dispersion-ultrasonic method on particle diameters and encapsulation efficiency of solid lipid nanoparticles of nicotinate-curcumin in order to obtain the process parameters resulting in smaller particle diameters and higher encapsulation efficiency .Methods: The content of nicotinate-curcumin was determined by HPLC.With the particle diameters and encapsulation efficiency of solid lipid nanoparticles of nicotinate -curcumin as the evaluation in-dicators , the process parameters of film dispersion-ultrasonic method were optimized by orthogonal experimental design and 95％confi-dence interval overlap method as the statistical analysis .Results:The optimum technological parameters of the solid lipid nanoparticles were as follows:the water bath temperature was 40℃and the rotation speed of eggplant bottle was 80 r· min-1 .The average particle size of solid lipid nanoparticles was 107.8 nm, polymer dispersity index ( PDI) was 0.583, and the encapsulation efficiency was 68.91％.Conclusion:The rotation speed of eggplant shaped bottle has notable influence on the particle diameters of solid lipid nanop -articles of nicotinate-curcumin prepared by film dispersion-ultrasonic method , while the water-bath temperature shows great influence on the encapsulation efficiency .Under the optimum conditions , it is possible to obtain the solid lipid nanoparticles with relatively smaller average particle diameters and higher encapsulation efficiency .

Objective To analyze the death status of children ≤ 5 years old in Jiaxing City from 2013 to 2017,and to provide scientific and effective measures of decreasing the children mortality and ensuring the health of children.Methods Death surveillance data of children ≤5 years old was obtained from monitoring network covering the whole city of maternal and child health information systems and the relevant maternal and child health statistics.The mortality rate,the sequence and changing trend of main death causes,prenatal health services of children ≤5 years old in Jiaxing City from 2013 to 2017were analyzed.Results From 2013 to 2017,there were 2 788 cases death of children ≤5 years old in Jiaxing City.The neonatal mortality rate (NMR),infant mortality rate (IMR),≤5 years old children mortality rate(U5MR) in Jiaxing City were 2.33‰,3.52‰ and 4.83 ‰,respectively.The mortality rates of all ages showed a declining trend year by year (x2NMR =19.641,P＜0.001;x2IMR =31.705,P ＜0.001;x2U5MR =48.294,P ＜0.001).There were significant differences in the mortality between the lower local and the migrant children (x22013 =26.16,x22014 =18.45,x22015 =27.72,x22016 =14.49,x22017=24.19;P＜0.001).The top two causes of death in children ≤ 5 years old were drowning,premature birth and low birth weight.The top two causes of death in infants and newborns were premature birth,low birth weight and other congenital anomalies.In the recent five years,49.60％ of children ≤5 years old died in the hospital.At the same time,the proportion of deaths on the way and at home was 15.64％ and 34.76％ respectively.Although there was a gap in the level of prenatal health services between local and mobile children,the gap has been declining year by year.Conclusions The key measures to decrease the mortality rate of children under 5 years old in Jiaxing City include strengthening the management of pregnancy care and high-risk pregnancy;paying attention to tertiary prevention and doing a good job in monitoring birth defects such as prenatal screening;enhancing safety education and child supervision for parents of children in 1-4 years old;reinforcing the construction of maternal and child health professional team and the technical training of newborn resuscitation techniques such as neonatal asphyxia recovery technology;intensifying the health-care and management of migrant children and improving the ability of parents to utilize child medical service.

[Objective] To analyze the clinical curative effect of 20G and 23G vitrectomy for posterior segment intraocular foreign bodies,to explore the differences of their efficacy and safety.[Methods] This was a retrospective case study.Select 71 patients (71 eyes) who suffered from posterior segment intraocular foreign bodies and underwent different ways of vitrectomy,according to the way of vitrectomy,the patients were enrolled into 20G vitrectomy group (20G group,37 patients,37 eyes) and 23G vitrectomy group (23G group,34 patients,34 eyes).All patients were given wound suture,and patients complicated traumatic cataract should underwent cataract surgery;then were given 20G/23G vitrectomy and extraction of intraction foreign bodies,and (or) be given retinal laser photocoagulation,cryocoagulation,and endotamponade during the procedure.Extraction of intraction foreign bodies and the location of retinal,surgical time,postoperative inflammation and stimulus syndrome,length of hospital stay,the best corrected acuity (BCVA) and other complications after surgery were registered.Minimum follow-up was 6 months.[Results] The rate of extraction of intraction foreign bodies and early retinal reattachment rate were 100％ of the two groups.Comparing the complications after surgery between the two groups,the differences had no statistical significance (all P ＞ 0.05) except the incidence of postoperative ocular hypotenison.The significant difference was found in the comparison of surgical time,average hospitalizcd days,postoperative inflammation score and stimulus syndrome between the two groups,and there were significant differences when the vision distribution before and after surgery in two groups were self-compared (P ＜ 0.05).At lastest follow up,the differences had no statistical significance when comparing the cases of unplanned surgical reoperation,the location of retinal and the vision distribution between the two groups (P ＞ 0.05).[Conclusion] 20G and 23G vitrectomy are both safely and effectively performed in patients with posterior segment intraocular foreign bodies,the efficacy and safety of them are comparable.There is higher incidence of postoperative ocular hypotension in 23G group,and it has an ascendant than 20G group in shorter surgical time and length of hospital stay,lighter postoperative inflamnation and stimulus syndrome.

Aim To explore the anti-proliferation effects of curcumin trinicotinate ( CurTn ) on vascular smooth muscle cell ( VSMC ) and its mechanism. Methods The cells were cultured in DMEM supple-mented with 10% fetal bovine serum. MTT assay was used to examine cell proliferation. FCM was used to observe cell cycle. The expressions of PCNA, Cy-clinD1 and p-ERK1/2 were analyzed using Western blot. Results CurTn could inhibit the proliferation of VSMC and showed a certain amount-time relationship. What’ s more, CurTn could increase the G1 phase pro-portion of cell, decrease the S phase proportion and the expression level of PCNA protein. It was also found that CurTn significantly inhibit the protein expression of p-ERK1/2 and Cyclin D1 . Conclusion CurTn may inhibit the proliferation of VSMC via downregulating the expression of CyclinD1 and p-ERK1/2 .